The Prognostic Role of Diagnostic Criteria for COVID-19-Associated Pulmonary Aspergillosis: A Cross-Sectional Retrospective Study.

Several criteria exist to diagnose pulmonary aspergillosis with varying degrees of certainty in specific populations, including oncohaematological patients (EORTC/MSG), ICU patients (mAspICU) and COVID-19 patients (ECMM). At the beginning of the pandemic, however, the diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA) could not be performed easily, and the decision to treat (DTT) was empirical. In this cross-sectional retrospective study including patients with SARS-CoV-2 infection and suspicion of CAPA, we studied the concordance between the DTT and the three diagnostic criteria using Cohen's coefficient, and then we identified the factors associated with the DTT and corrected them by treatment to study the influence of the diagnostic criteria on survival. We showed good concordance of the DTT and mAspICU and ECMM criteria, with "compatible signs", "positive culture" and "positive galactomannan" influencing the DTT. Treatment also showed a positive effect on survival once corrected for a putative, possible or probable diagnosis of CAPA using mAspICU and ECMM criteria. We conclude that EORTC/MSGERC are not considered applicable in clinical practice due to the lack of inclusion of signs and symptoms and do not lead to improved survival. mAspICU and ECMM criteria showed a good degree of agreement with the DTT and a positive correlation with patient recovery.

Outbreak of Candida parapsilosis fungemia in an intensive care unit during a COVID surge: an epidemic within a pandemic.

We sought to investigate epidemiology, risk factors, clinical features, and outcome of the C. parapsilosis blood stream infection (BSI) outbreaks observed during the first surges of COVID-19 pandemic in our population. Retrospective, monocentric observational study in the 24 bed intensive care unit (ICU) of a tertiary care medical center in northern Italy, from 2019 to 2021 first 5 months. 2030 patients were enrolled, of whom 239 were COVID-19 positive. The total incidence of Candida-BSI was 41.9 per 1000 admissions, with two outbreaks during 2020 spring and winter's COVID surges. The total numbers of C. parapsilosis BSI cases are 94, of which 21 during the first outbreak and 20 during the second. In our population, COVID-19 was strongly associated with C. parapsilosis BSI (OR 4.71, p < 0.001), as well as continuous renal replacement therapy (CRRT) (OR 3.44, p = 0.001), prolonged antibiotic therapy (OR 3.19, p = 0.004), and delayed infusion sets replacements (OR 2.76, p = 0.015). No statistically significant association was found between Candida-BSI episodes and mortality, when adjusted for other known outcome risk factors. COVID surges undermined the infectious control measures in our ICU, leading to two outbreak of C. parapsilosis BSI. A stricter, thorough management of intravascular devices and infusion set is crucial in prevention of catheter related BSI, and awareness must be kept high, especially in emergencies circumstances, such as the ongoing COVID-19 pandemic.

Superior vena cava Candida krusei septic thrombophlebitis in an ARDS patient on ECMO, with an unusual late complication.

Candida-related bloodstream infections (BSIs) represent a severe condition associated with health care in the critical patient, with an increasing incidence of Candida non-albicans species. These infections could lead to several and unusual complications in high-risk patients due to various factors, including a prolonged hospital stay and invasive medical interventions. Here we report a case of a Candida krusei septic thrombophlebitis in an ARDS patient admitted to the ICU, complicated by a late onset prostatic abscess. To our knowledge, our patient represents the first reported case of a prostatic abscess due to Candida krusei treated with pharmacological therapy alone.

Yeast Bloodstream Infections in the COVID-19 Patient: A Multicenter Italian Study (FiCoV Study).

Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0-93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis.

Catheter-related blood stream infection caused by Millerozyma farinosa in an immunocompetent patient: a case report and a brief review of the literature.

Millerozyma farinose is a halotolerant yeast that has recently been described as an emerging human pathogen, especially in immunocompromised patients. Both the diagnostic process and treatment options are still unclear. Here, we report a case of an immunocompetent oncological patient who developed a catheter-related bloodstream infection (CRBSI) with a concomitant respiratory tract infection caused by M. farinosa. In this report, we discuss how prompt microbiological identification and attentive evaluation of the patient's clinical status can play a significant role in the appropriate management of infections caused by uncommon fungi. MALDI-TOF technology has also substantially improved the timely diagnosis of rare fungi. Furthermore, our diagnosis was subsequently confirmed by 5.8S rRNA sequencing. In our patient, the rapid diagnosis of fungaemia was crucial, together with catheter removal and the initiation of antifungal treatment, for the patient's clinical improvement.

A Case Report of Disseminated Histoplasmosis in AIDS Diagnosed Through Peripheral Blood Smear.

BACKGROUND: Histoplasma capsulatum is an environmental fungus that causes opportunistic infections in AIDS patients in endemic areas but is uncommon in Europe. It shares clinical features with other opportunistic infections and lymphoproliferative disorders common in AIDS patients. The World Health Organization included Histoplasma antigen tests on the Lists of Essential In Vitro Diagnostics, however, they are not routinely available in non-endemic countries. Consequently, mycoses can be a great challenge for clinicians in non-endemic countries. CASE PRESENTATION: We report the case of a 42-year-old Colombian woman admitted to an Italian university hospital with diarrhea, acute renal failure, psychomotor impairment and fever. When a screening HIV test came back positive, she was screened for opportunistic infections with no results. Given the severity of her clinical condition a broad spectrum antibacterial and antifungal therapy was started in addition to HAART. A blood smear documented leucocytes inclusions, identified as capsular structures. On suspicion of Histoplasma capsulatum the patient was started on empiric amphotericin B. The diagnosis was confirmed by positive serology. Despite therapy, the patient died shortly after. In the following days, the mycology laboratory managed to grow Histoplasma capsulatum, thus confirming the diagnosis of invasive histoplasmosis in AIDS. CONCLUSION: The case highlights the need for a high index of suspicion for the diagnosis of endemic mycosis outside of endemic areas, and the necessity of expanding access to tests. Even if antigen/ antibody tests are not available, however, blood smear has worldwide feasibility and allows a rapid diagnosis.

Azole resistance in Aspergillus isolates by different types of patients and correlation with environment - An Italian prospective multicentre study (ARiA study).

BACKGROUND: A wide range of frequency of azole-resistance in A fumigatus in different patient populations worldwide was observed threatening to reduce therapeutic options. OBJECTIVES: Estimate the prevalence of azole-resistance, investigate the molecular mechanisms of resistance, compare the genotypes of resistant clinical isolates with those from the surrounding environment. METHODS: Aspergillus isolates were collected by seven Italian hospital microbiology laboratories. Strains were isolated from different clinical samples from unselected patients. The azole-resistance was evaluated using screening test and microdilution EUCAST method. The molecular mechanism of resistance was performed sequencing the cyp51A gene. Resistant isolates were genotyped by microsatellite analysis and their profiles compared with those of azole-resistant isolates from previous Italian studies. RESULTS: 425 Aspergillus isolates from 367 patients were analysed. The azole-resistance rates were 4.9% and 6.6% considering all Aspergillus spp. isolates and the A fumigatus sensu stricto, respectively. All resistant isolates except one were from a single hospital. Two rare azole-resistant species were identified: A thermomutatus and A lentulus. The predominant resistance mechanism was TR34 /L98H. No correlation between the clinical resistant strains and environmental isolates from patients' home/work/ward was observed. The analysis of the molecular correlation between the resistant clinical strains collected in the present study and those of environmental and clinical origin collected in previous Italian studies reveals a progressive diversification of azole-resistant genotypes starting from a founder azole-resistant genotype. CONCLUSIONS: This study confirms the trend of azole-resistance rate in Italy, showing a geographical difference. Data reinforce the importance of surveillance programmes to monitor the local epidemiological situation.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Yeast-like filamentous fungi: Molecular identification and in vitro susceptibility study.

Yeast-like filamentous fungi, collected in Italy from 1985 to 2018, were submitted to molecular identification and antifungal susceptibility testings. Clinical isolates were identified as Magnusiomyces capitatus (28), M. clavatus (18), and Geotrichum candidum (2). M. clavatus was prevalent among blood isolates (18/24), M. capitatus among isolates from other biological materials. The intrinsic echinocandin resistance was confirmed. Both species had low minimum inhibitory concentrations (MICs) of itraconazole, posaconazole, and voriconazole, while M. clavatus had lower MIC of flucytosine and higher MIC of isavuconazole than M. capitatus. The intrinsic resistance of these species to echinocandins could be the reason of the recent increase of M. clavatus bloodstream infections.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a low-grade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Presence of L701 M mutation in the FKS1 gene of echinocandin-susceptible Candida krusei isolates.

Resistance of Candida krusei isolates to echinocandins, the recommended drugs to treat candidemia, has been associated with mutations in hot spot (HS) regions of the FKS1 gene or L701 M mutation in a region between HS1 and HS3 of FKS1. However, the role of L701 M mutation alone in causing reduced echinocandins susceptibility is still unclear. We analyzed a region between HS1 and HS3 of FKS1 of 25 C. krusei isolates from clinical samples. Susceptibility to echinocandins was determined by a commercial broth microdilution assay and by the microdilution method according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The L701 M mutation was detected in 22/25 (88%) C. krusei isolates with low MIC values in the absence of other HS mutations. The presence of isolated L701 M mutation in C. krusei clinical isolates susceptible to echinocandins suggests that this mutation may be just associated to polymorphism in the C. krusei population.

CAND-LO 2014-15 study: changing epidemiology of candidemia in Lombardy (Italy).

PURPOSE: The aim of this study was to monitor recent changes in the epidemiology of candidemia and in the antifungal susceptibility profiles of Candida isolates in one Italian region (Lombardy) in 2014-2015 in comparison with two other studies performed in the same area in 1997-1999 and in 2009. METHODS: A laboratory-based surveillance was conducted in 11 microbiology laboratories. Identification of Candida isolates from 868 episodes and antifungal susceptibility testing (YeastOne) was performed locally. RESULTS: A progressive increase in the rate of candidemia up to 1.27/1000 admissions and 1.59/10,000 patient days was documented. In all the three surveys, Candida albicans remains the most frequently isolated species, ranging from 52 to 59 % of the etiology of BSIs. The epidemiological shift to the more resistant C. glabrata, observed between 1997-1999 and 2009 surveys, was not confirmed by our more recent data. The pattern of etiology of BSIs occurred in 2014-2015 overlaps that of the 90s. Acquired antifungal resistance is a rare event. No isolate had an amphoterin B minimal inhibitory concentration (MIC, mg/L) value higher than the epidemiological cutoff. All the echinocandin MIC distributions are typical for wild-type organisms except for those of two C. glabrata isolates. Fluconazole resistance declined from 24.9 % in the 2009 survey to 5.4 % in the recent one. CONCLUSIONS: Data from regional surveys may highlight the influence of therapeutic practices on the epidemiology of Candida BSIs and may optimize empirical therapies.

Acute isolated appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia.

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment with voriconazole was promptly started with success. No other site of Aspergillus localization was detected. Appendicitis is rarely caused by fungal organisms and isolated intestinal aspergillosis without pulmonary infection is unusual. To our knowledge, this is the first report of infection due to A. carneus in a child and in a primary gastrointestinal infection.

Invasive fungal rhinosinusitis in adult patients: Our experience in diagnosis and management.

BACKGROUND: This paper describes our experience in the management of acute and chronic invasive fungal rhinosinusitis (IFRS) in adults. METHODS: Medical files of all patients aged >18 years treated in our institutions for IFRS from 2002 to 2013 were retrospectively reviewed. RESULTS: A total of 18 cases (10 acute and 8 chronic) were recorded. In acute form, haematological malignancies represented the principal comorbidity (100%), while in chronic form this was diabetes mellitus (87.5%). All patients received systemic antifungal agents. Endoscopic sinus surgery was performed in 16/18 patients (88.9%). Among patients with an acute IFRS, 4/10 died of fungal infection (40%), on the other side 2/8 patients with chronic IFRS died of the evolution of the mycosis (25%). CONCLUSIONS: Acute and chronic IFRS are different entities: in acute form, prognosis is poor, so therapy should be promptly performed, although host immune status and evolution of the haematological disease are key factors for the outcome. In chronic form, a wide surgical excision of the disease is recommended in order to obtain a complete removal of fungal infection. In both forms, early clinical findings are non-specific and ambiguous, so diagnosis depends on a high index of suspicion, taking into account predisposing factors.

Allergic fungal rhinosinusitis due to Curvularia lunata.

We report a case of Curvularia lunata infection in an immunocompetent male with an initial diagnosis of suspected left side allergic fungal rhinosinusitis (AFRS), treated surgically. He had a relapse of nasal polyposis and underwent a surgical revision under local anaesthesia with endoscopic nasal polypectomy. The histological examination of the surgical specimen showed an inflammatory polyp of the paranasal sinuses, with eosinophil and lymphocyte infiltration, but without evidence of fungi. However, Curvularia spp fungus grew in cultures of nasal sinus drainage and bioptical specimens. The fungus was identified by DNA sequencing as C. lunata. The patient was then treated with itraconazole (200 mg BID for 4 weeks), mometasone furoate nasal spray (100 mcg BID for 6 months) and normal saline nasal irrigations. At the last follow-up endoscopic evaluation after 19 month from treatment, the patient was symptomless and free from disease. No polyp recurrence nor seromucous discharges were noticed. This first case of C. lunata-associated AFRS reported in Italy, highlights the difficulty of this diagnosis and the usefulness of molecular identification of the fungal species involved.

Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006-2008).

Critically ill patients admitted to intensive care units (ICU) are highly susceptible to healthcare-associated infections caused by fungi. A prospective sequential survey of invasive fungal infections was conducted from May 2006 to April 2008 in 38 ICUs of 27 Italian hospitals. A total of 384 fungal infections (318 invasive Candida infections, three cryptococcosis and 63 mould infections) were notified. The median rate of candidaemia was 10.08 per 1000 admissions. In 15% of cases, the infection was already present at the time of admission to ICU. Seventy-seven percent of Candida infections were diagnosed in surgical patients. Candida albicans was isolated in 60% of cases, Candida glabrata and Candida parapsilosis in 13%, each. Candida glabrata had the highest crude mortality rate (60%). Aspergillus infection was diagnosed in 32 medical and 25 surgical patients. The median rate was 6.31 per 1000 admissions. Corticosteroid treatment was the major host factor. Aspergillosis was demonstrated to be more severe than candidiasis as the crude mortality rate was significantly higher (63% vs. 46%), given an equal index of severity, Simplified Acute Physiology Score (SAPS-II). The present large nationwide survey points out the considerable morbidity and mortality of invasive fungal infections in surgical as well as medical patients in ICU.

Cross-reactivity of Fusarium spp. in the Aspergillus Galactomannan enzyme-linked immunosorbent assay.

Nine of 11 hematological patients with disseminated/deep-seated Fusarium infection tested at least twice for Aspergillus galactomannan (GM) had repeated positive results in the absence of Aspergillus isolation in culture. The centrifuged supernatants of 12 Fusarium isolates were tested by a GM enzyme-linked immunosorbent assay (EIA). All the isolates produced positive reactions when tested undiluted. These results show cross-reactivity of Fusarium spp. with Aspergillus GM that may constitute a drawback with respect to the specificity of the Platelia EIA.

Sphenoid sinus fungus ball: our experience.

BACKGROUND: Fungal rhinosinusitis is a common disease of the paranasal sinuses. The fungus ball (FB) is defined as an extramucosal mycotic proliferation that fills one or more paranasal sinuses. Sphenoid sinus is an uncommon localization of this disease, as reported in the literature. This study describes our experience in the diagnosis and treatment of sphenoid sinus FB (SSFB), with a particular focus on the surgical approach to the sphenoid sinus. METHODS: We retrospectively analyzed the clinical records of patients affected by FB of the sphenoid sinus, who underwent endoscopic sinus surgery (ESS) in our institutions between 1995 and 2009. We described the surgical technique, the methods of mycological and histopathological evaluation, as well as the perioperative and postoperative management. RESULTS: From 1995 to 2009, 226 patients affected by sinonasal FB underwent ESS in our institutions. A sphenoid localization was found in 56 patients (24.78%; mean age, 62 years). Cephalea was the most common symptom, and 14.3% of patients complained of ocular symptoms. We performed a direct paraseptal sphenoidotomy in 31 patients (55.4%) and a transethmoidal sphenoidotomy in 25 patients (44.6%). Histology unveiled fungal hyphae with absent mucosal invasion in all cases. Cultural results revealed positivity for mycotic colonization in 26 cases (46.4%, most commonly Aspergillus fumigatus). Follow-up ranged from 12 to 181 months with a mean of 70.7 months. CONCLUSION: The description of our experience in the diagnosis and treatment of SSFB underlines the importance of a precise diagnostic pathway in case of sphenoidal disease. Nowadays, in our opinion, the paraseptal direct sphenoidotomy represents the less invasive, fastest and most anatomically conservative approach to the sphenoid sinus in case of SSFB.

Retroperitoneal cryptococcoma in a case of disseminated cryptococcosis on antifungal maintenance therapy.

Cryptococcoma is a rare entity, characterized by solid, space-occupying masses, usually found in the brain. It has been reported in the setting of "paradoxical" immune reconstitution inflammatory syndrome. A case of retroperitoneal cryptococcoma in a HIV-infected woman with a clinical history of disseminated cryptococcosis on antifungal maintenance therapy is described.